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TY - JOUR

T1 - HIV-1 envelope diversity 1 year after seroconversion predicts subsequent disease progression

AU - Rachinger, Andrea

AU - Kootstra, Neeltje A.

AU - Gijsbers, Esther F.

AU - van den Kerkhof, Tom L. G. M.

AU - Schuitemaker, Hanneke

AU - van 't Wout, Angélique B.

PY - 2012

Y1 - 2012

N2 - Objective: Recent studies have suggested that the dynamics of HIV-1 evolutionary rate reflect the rate of disease progression. We wished to determine whether viral diversity early in infection is predictive of the subsequent disease course. Design: HIV-1 envelope diversity at seroconversion and 1 year thereafter from 89 homosexual participants of the Amsterdam Cohort Studies on HIV infection and AIDS was correlated with clinical endpoints and markers of disease progression. Methods: Heteroduplex mobility assay (HMA) and sequencing followed by calculation of pairwise genetic distances were applied to determine HIV-1 envelope diversity. The HMA pattern (presence or absence of heteroduplexes) and sequence diversity were each tested for correlation with the clinical course of infection. Results: HMA pattern at 1-year postseroconversion was significantly associated with progression to AIDS and AIDS-related death, with presence of heteroduplexes associated with accelerated disease progression. Moreover, not only this dichotomous measure of viral diversity (absence or presence of heteroduplexes), but also genetic diversity itself was associated with disease course. HMA pattern was an independent predictor of accelerated disease progression, also when CCR5 genotype, human leukocyte antigen (HLA)-type, viral load, CD4(+) T-cell counts, and coreceptor use at viral load set point were included in the analysis. Conclusion: Viral diversity early in HIV-1 infection is predictive of the subsequent disease progression. It remains to be established whether viral diversity itself plays a causal role in the increased damage to the immune system or whether it is a reflection of immune pressure or other selective forces. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

AB - Objective: Recent studies have suggested that the dynamics of HIV-1 evolutionary rate reflect the rate of disease progression. We wished to determine whether viral diversity early in infection is predictive of the subsequent disease course. Design: HIV-1 envelope diversity at seroconversion and 1 year thereafter from 89 homosexual participants of the Amsterdam Cohort Studies on HIV infection and AIDS was correlated with clinical endpoints and markers of disease progression. Methods: Heteroduplex mobility assay (HMA) and sequencing followed by calculation of pairwise genetic distances were applied to determine HIV-1 envelope diversity. The HMA pattern (presence or absence of heteroduplexes) and sequence diversity were each tested for correlation with the clinical course of infection. Results: HMA pattern at 1-year postseroconversion was significantly associated with progression to AIDS and AIDS-related death, with presence of heteroduplexes associated with accelerated disease progression. Moreover, not only this dichotomous measure of viral diversity (absence or presence of heteroduplexes), but also genetic diversity itself was associated with disease course. HMA pattern was an independent predictor of accelerated disease progression, also when CCR5 genotype, human leukocyte antigen (HLA)-type, viral load, CD4(+) T-cell counts, and coreceptor use at viral load set point were included in the analysis. Conclusion: Viral diversity early in HIV-1 infection is predictive of the subsequent disease progression. It remains to be established whether viral diversity itself plays a causal role in the increased damage to the immune system or whether it is a reflection of immune pressure or other selective forces. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

U2 - 10.1097/QAD.0b013e328354f539

DO - 10.1097/QAD.0b013e328354f539

M3 - Article

C2 - 22555160

VL - 26

SP - 1517

EP - 1522

JO - AIDS (London, England)

JF - AIDS (London, England)

SN - 0269-9370

IS - 12

ER -